8-115409708-A-C

Position:

• chr8-115409708-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014112.5(TRPS1):​c.*4315T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,816 control chromosomes in the GnomAD database, including 26,844 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.58 (26840 hom., cov: 32)
  • Exomes 𝑓: 0.44 (4 hom.)
• Consequence: TRPS1 NM_014112.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161

Genes affected

TRPS1 (HGNC:12340): (transcriptional repressor GATA binding 1) This gene encodes a transcription factor that represses GATA-regulated genes and binds to a dynein light chain protein. Binding of the encoded protein to the dynein light chain protein affects binding to GATA consensus sequences and suppresses its transcriptional activity. Defects in this gene are a cause of tricho-rhino-phalangeal syndrome (TRPS) types I-III. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPS1	NM_014112.5	c.*4315T>G		3_prime_UTR_variant	7/7	ENST00000395715.8
TRPS1	NM_001282902.3	c.*4315T>G		3_prime_UTR_variant	6/6
TRPS1	NM_001282903.3	c.*4315T>G		3_prime_UTR_variant	7/7
TRPS1	NM_001330599.2	c.*4315T>G		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPS1	ENST00000395715.8	c.*4315T>G		3_prime_UTR_variant	7/7	1	NM_014112.5	A1
TRPS1	ENST00000640765.1	c.*4315T>G		3_prime_UTR_variant	6/6	2		P4

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87786 AN: 151664 Hom.: 26789 Cov.: 32

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.524

GnomAD4 exome AF: 0.438 AC: 14 AN: 32 Hom.: 4 Cov.: 0 AF XY: 0.455 AC XY: 10 AN XY: 22

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.423

GnomAD4 genome AF: 0.579 AC: 87896 AN: 151784 Hom.: 26840 Cov.: 32 AF XY: 0.575 AC XY: 42608 AN XY: 74156

Gnomad4 AFR AF: 0.784

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.575

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.520

Alfa AF: 0.504 Hom.: 39943

Bravo AF: 0.597

Asia WGS AF: 0.559 AC: 1943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs800897; hg19: chr8-116421936;